Interleukin-8 in alcoholic liver disease

Acute alcoholic hepatitis is accompanied by features of the acute phase response, peripheral blood neutrophilia and liver neutrophil infiltrate even in the absence of demonstrable bacterial or fungal infection. Plasma levels of tumour necrosis factor (TNF) and interleukin-6 (IL-6), the major cytokine inducers of the acute phase response, are markedly raised in acute alcoholic hepatitis and correlate closely with clinical and laboratory indicators of disease severity. The potent neutrophil activator and chemotaxin interleukin-8 (IL-8) is released in response to TNF and recent interest has focussed on its possible role in producing the characteristic peripheral blood neutrophilia and liver neutrophil infiltrate in alcoholic hepatitis. Circulating IL-8 and liver tissue levels of IL-8 are markedly raised in alcoholic hepatitis, with highest levels in patients who die within the first four weeks of admission to hospital. There is a close correlation between hepatic IL-8 and infiltration with neutrophils. Less dramatic increases in circulating IL-8 are present in abstinent alcoholic cirrhotics and patients admitted for detoxification. These observations suggest a central role for IL-8 in the neutrophilia and hepatic neutrophil infiltrate characteristic of acute alcoholic hepatitis.